Department of Pathology and Forensic Medicine, College of Basic Medical Science, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Department of Pathology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang 310000, P.R. China.
Oncol Rep. 2021 Nov;46(5). doi: 10.3892/or.2021.8187. Epub 2021 Sep 16.
Ubiquilin‑1 (UBQLN1) is an essential factor for the maintenance of proteostasis in cells. It is important for the regulation of different protein degradation mechanisms, including the ubiquitin‑proteasome system, autophagy and endoplasmic reticulum‑associated protein degradation pathways. However, the role of UBQLN1 in cancer progression remains largely unknown. In the present study, the expression, functions and molecular mechanisms of UBQLN1 in breast cancer tissue samples and cell lines were explored. Immunohistochemical and bioinformatics analyses revealed that UBQLN1 expression was significantly upregulated in breast cancer tissues and cell lines. UBQLN1 expression in breast cancer was significantly associated with lymph node metastasis and TNM stage. Moreover, a high UBQLN1 expression was a predictor of an unfavorable survival in patients with breast cancer. , UBQLN1 silencing markedly inhibited cell migration and invasion, epithelial‑to‑mesenchymal transition (EMT) and MMP expression. UBQLN1 silencing attenuated the stem cell‑like properties of breast cancer cells, including their mammosphere‑forming abilities. UBQLN1 knockdown also enhanced breast cancer cell chemosensitivity to paclitaxel. The expression levels of the stem cell markers. Aldehyde dehydrogenase 1 (ALDH1), Oct‑4 and Sox2 were significantly decreased in the cells in which UBQLN1 was silenced, whereas breast cancer stem cells exhibited an increased expression of UBQLN1. Mechanistically, UBQLN1 knockdown inhibited the activation of AKT signaling, as revealed by the increased PTEN expression and the decreased expression of phosphorylated AKT in cells in which UBQLN1 was silenced. On the whole, the present study demonstrates that UBQLN1 is aberrantly upregulated in breast cancer and predicts a poor prognosis. The silencing of UBQLN1 inhibited the invasion, EMT and stemness of breast cancer cells, possibly via AKT signaling.
泛素结合酶 1（UBQLN1）是细胞中维持蛋白质平衡的必需因素。它对于不同蛋白降解机制的调节非常重要，包括泛素-蛋白酶体系统、自噬和内质网相关蛋白降解途径。然而，UBQLN1 在癌症进展中的作用在很大程度上仍不清楚。本研究探讨了 UBQLN1 在乳腺癌组织样本和细胞系中的表达、功能和分子机制。免疫组织化学和生物信息学分析显示，UBQLN1 在乳腺癌组织和细胞系中的表达显著上调。UBQLN1 在乳腺癌中的表达与淋巴结转移和 TNM 分期显著相关。此外，UBQLN1 高表达是乳腺癌患者预后不良的预测因子。沉默 UBQLN1 显著抑制细胞迁移和侵袭、上皮-间充质转化（EMT）和 MMP 表达。UBQLN1 沉默减弱了乳腺癌细胞的干细胞样特性，包括其形成乳腺球体的能力。UBQLN1 敲低还增强了乳腺癌细胞对紫杉醇的化疗敏感性。干细胞标志物的表达水平。醛脱氢酶 1（ALDH1）、Oct-4 和 Sox2 在沉默 UBQLN1 的细胞中显著降低，而乳腺癌干细胞则表现出 UBQLN1 的高表达。在机制上，沉默 UBQLN1 抑制了 AKT 信号的激活，这表现为沉默 UBQLN1 的细胞中 PTEN 表达增加和磷酸化 AKT 表达减少。总的来说，本研究表明 UBQLN1 在乳腺癌中异常上调，并预测预后不良。沉默 UBQLN1 抑制了乳腺癌细胞的侵袭、EMT 和干细胞特性，可能通过 AKT 信号通路。
